Fear is a normal reaction to danger, but when fear responses are routinely expressed inappropriately, a fear or anxiety disorder exists. Many of the stimuli that activate fear responses in humans are learned about through experience. The proposed research is thus aimed at understanding how the brain learns and stores information about threats. Classical fear conditioning is used as a behavioral procedure through which an innocuous stimulus (a conditioned stimulus), when associated with an aversive event (an unconditioned stimulus), acquires the capacity to elicit fear reactions. The hypothesis being tested is that the amygdala plays an essential role in the plasticity that underlies fear conditioning. This hypothesis is supported by considerable evidence, but some fundamental questions concerning its validity remain unanswered. Furthermore, much remains unknown about the mechanisms within the amygdala that contribute to fear conditioning. Two groups of studies will be performed. The first group involves research on the neural system involved in fear conditioning. The aims are to clarify issues concerning the neural pathways by which an acoustic conditioned stimulus is transmitted to the amygdala, the patterns of information flow within the amygdala, the necessity of the amygdala for the acquisition and storage process and the nature of neural coding in various components of the circuitry. The second group pursues questions about the cellular and molecular mechanisms involved. The aims are to examine the physiology and morphology of excitatory amino acid receptor function in the sensory input pathways to the amygdala and to determine the role of these receptors in synaptic plasticity and fear conditioning. In addition, studies are planned to examine the role of protein and RNA synthesis and the cAMP cascade in synaptic plasticity and fear conditioning. Together, these studies represent an integrated, multidisciplinary research program aimed at understanding the nature of fear and will hopefully provide information that will be useful in preventing or treating fear disorders.